This is a revised K02 application. Dr. Stephen L. Dewey is a neuroanatomist and a senior scientist. He has a distinguished record in neuroimaging, microdialysis and medications development for drug abuse. His early work focused on imaging neurotransmitter interactions. These pioneering studies produced a paradigm shift that represents one of the most effective applications of PET research today. As a result, Dr. Dewey identified gamma vinyl-GABA, (GVG, vigabatrin) for the treatment of drug abuse. Following the generation of an unprecedented published preclinical database, which produced 9 U.S. patents (1 additional pending), he designed and conducted 2 open labeled clinical trials in adult cocaine and methamphetamine abusers. These trials suggested clinical efficacy and demonstrated visual safety, while also serving as the foundation for 2 Investigative New Drug (IND) applications, recently accepted by the FDA, for Phase I and II clinical trials. Dr. Dewey has successfully graduated 3 doctoral students and is currently a thesis advisor for three additional doctoral candidates as well as being a mentor to several junior scientists. In 1994, Dr. Dewey initiated an outreach program to adolescents that reached more than 55,000 children last year alone (more than 300,000 since its inception), motivating his new research initiative in inhalant abuse. This K02 will release Dr. Dewey from teaching and provide 60% salary support, which will result in at least 75% protected time to focus on the new molecular entity, S- (+)-GVG, for the treatment of adult and adolescent methamphetamine or inhalant abuse. This application proposes 2 synergistic goals: (1) Research (60%); to identify optimal treatment regimens with the new molecular entity, S- (+)-GVG, for adult and adolescent methamphetamine or inhalant abuse using the identical strategies he successfully employed with GVG and (2); Mentoring and outreach (15%): to mentor junior investigators, post-doctoral fellows, and graduate and undergraduate students while continuing his extensive outreach program. This research benefits from collaborators at BNL, Stony Brook Univ, New York Univ, St. Johns Univ, and NIDA intramural. Thus, the objectives of this application are to identify optimal treatment regimens for methamphetamine or inhalant abuse while inspiring, teaching, and encouraging young scientists across disciplines to investigate the major public health consequences created by adolescent and adult drug abuse. [unreadable] [unreadable] [unreadable]